Chemical probes for investigating protein liquid-liquid phase separation and aggregation |
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Institution: | 1. CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, China;2. Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China;3. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200030, China;4. Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China;5. WLA Laboratories, World Laureates Association, Shanghai 201203, China;1. German Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, 37075 G?ttingen, Germany;2. Department for NMR-based Structural Biology, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, 37077 G?ttingen, Germany |
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Abstract: | Protein liquid-liquid phase separation drives the dynamic assembly of membraneless organelles for fulfilling different physiological functions. Under diseased condition, protein may undergo liquid-to-solid condensation to form pathological amyloid aggregates closely associated with neurodegenerative diseases. Chemical probe serves as an important chemical tool not only for exploring the basic principle of the dynamic assembly of different protein condensates in vitro and in cell but also for clinical diagnosis and therapeutics of the related diseases. In this review, we first introduce chemical probes to image and regulate protein condensates. Then, we summarized three different categories of chemical probes including general amyloid dye, selective positron emission tomography tracer, and disaggregating binder, which feature distinct interaction pattern and activity upon binding to different pathological amyloid fibrillar aggregates. Next, we discuss the development of chemical probes for tracking protein amorphous aggregates in cells. Finally, we point out future direction in expanding the probes’ chemical space and applications. |
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Keywords: | Chemical probes Protein liquid-liquid phase separation (LLPS) Amyloid aggregation Neurodegenerative diseases Protein condensation PET tracer Fluorescence imaging |
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